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Introduction: This study presents our online-teaching material within the k-MED project (Knowledge in Medical Education) at the university of Marburg. It is currently organized in five e-learning modules: cytogenetics, chromosomal aberrations, formal genetics, fundamentals of molecular diagnostics, and congenital abnormalities and syndromes. These are basic courses intended to do the educational groundwork, which will enable academic teachers to concentrate on more sophisticated topics during their lectures. Methods: The e-learning modules have been offered to a large group of about 3300 students during four years at the Faculty of Medicine in Marburg. The group consists of science students (human biology) and medical students in the preclinical or the clinical period, respectively. Participants were surveyed on acceptance by evaluating user-tracking data and questionnaires. Results and Conclusion: Analysis of the evaluation data proofs the broad acceptance of the e-learning modules during eight semesters. The courses are in stable or even increasing use from winter term 2005/06 until spring term 2009. Conclusion: Our e-learning-model is broadly accepted among students with different levels of knowledge at the Faculty of Medicine in Marburg. If the e-learning courses are maintained thoroughly, minor adaptations can increase acceptance and usage even furthermore. Their use should be extended to the medical education of technical assistances and nurses, who work in the field of human genetics. Keywords: Human genetics, e-Learning, evaluation, multimedia
Einleitung: Die vorliegende Studie beschreibt unser Online-Lehrmaterial Humangenetik im Zusammenhang mit dem k-MED-Projekt (Knowledge in Medical Education) an der Philipps-Universität Marburg. Es besteht aus fünf E-Learning-Modulen: Zytogenetik, Chromosomenstörungen, Formalgenetik, Grundlagen der molekularen Diagnostik sowie Kongenitale Abnormitäten und Fehlbildungssyndrome. Diese E-Module sollen ein einheitliches Wissensniveau der Studierenden gewährleisten und die Dozenten in der Präsenzlehre entlasten. Methoden: Die fünf E-Learning-Module Humangenetik wurden auf freiwilliger Basis einer großen Personengruppe von ca. 3300 Studierenden am Fachbereich Humanmedizin der Universität Marburg über eine Dauer von vier Jahren angeboten. Die Teilnehmer bestanden aus Naturwissenschaftlern (Humanbiologie) im 5. Fachsemester und Studierenden der Humanmedizin, die sich entweder in der Vorklinik (1. Semester) oder im klinischen Studienabschnitt (7./8. Semester) befanden. Von diesen wurden Daten zur Akzeptanz in Form von Usertrackingdaten und klausur-begleitenden Fragebögen erhoben. Ergebnisse und Schlussfolgerung: Die Evaluation zeigte eine breite Akzeptanz unserer Lehrmodule über einen Zeitraum von acht Semestern. Obwohl das Angebot freiwillig ist, werden die Online-Kurse Humangenetik konstant oder sogar in zunehmendem Maße zwischen Wintersemester 2005/06 und Sommersemester 2009 genutzt. Fazit: Unser E-Learning-Modell Humangenetik wird von Studierenden aus unterschiedlichen Semestern und Studiengängen am Fachbereich Humanmedizin gut angenommen und genutzt. Bei sorgfältiger Pflege der Online-Kurse steigern moderate Anpassungen sowohl Akzeptanz als auch Benutzungshäufigkeit in signifikanter Weise. Die Anwendung der E-Learning Module erscheint uns auch in der Ausbildung von MTAs oder Pflegekräften sinnvoll, um ein ausreichendes Grundwissen in Humangenetik zu gewährleisten. Schlüsselwörter: Humangenetik, Evaluation, Multimedia, E-Learning
Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats.
Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed.
Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling.
Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.
PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells
(2011)
PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.
The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling. Keywords: Acute Myeloid Leukemia (AML), Allogeneic Stem Cell Transplantation (SCT), Indication, Cytogenetics, Polymerase Chain Reaction (PCR)
Background: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed ‘chronic cerebrospinal venous insufficiency’ (CCSVI) was proposed, provoking significant attention in the media and scientific community.
Methods: Twenty MS patients (mean age 42.2±13.3 years; median Extended Disability Status Scale 3.0, range 0–6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA≤0.3 cm2 indicated ‘stenosis,’ and IJV-VCSA decrease from supine to upright position ‘reverted postural control.’ The sonographer, data analyser and statistician were blinded to the patient/control status of the participants.
Results: No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA≤0.3 cm2 was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI.
Conclusions: This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.
The ability to escape apoptosis or programmed cell death is a hallmark of human cancers, for example pancreatic cancer. This can promote tumorigenesis, since too little cell death by apoptosis disturbs tissue homeostasis. Additionally, defective apoptosis signaling is the underlying cause of failure to respond to current treatment approaches, since therapy-mediated antitumor activity requires the intactness of apoptosis signaling pathways in cancer cells. Thus, the elucidation of defects in the regulation of apoptosis in pancreatic carcinoma can result in the identification of novel targets for therapeutic interference and for exploitation for cancer drug discovery. Keywords: apoptosis; pancreatic cancer; TRAIL; IAPs; mitochondria
Novel insights into the synergistic interaction of Bortezomib and TRAIL: tBid provides the link
(2011)
The proteasome inhibitor Bortezomib has been identified as a potent enhancer of TRAIL-induced apoptosis in several human cancers. However, the identification of the underlying molecular mechanisms of this synergistic cell death induction has been ongoing over the last years. A recent study identifies a new mechanism of action for the synergism of TRAIL and Bortezomib.
Background: Working conditions of nursery school teachers have not been scrutinized thoroughly in scientific research. Only a few studies have so far examined work-load and strain in this profession. Preferably, subjective perceptions should be corroborated by data that can be quantified more objectively and accurately. The aim of the present observational field study was to evaluate pedagogical staffs' workflow.
Methods: In 2009 eleven educators in a day care centre were observed throughout three complete workdays. A total of 250 working hours were recorded.
Results: An educators' workday lasted on average 07:46:59 h (SD = 01:01:10 h).Within this time span, an average of 02:20:46 h (30.14%, SD = 00:28:07 h) were spent on caring, 01:44:18 h on playing (22.33%, SD = 00:54:12 h), 00:49:37 h on educational work (10.62%, SD = 00:40:09), and only 00:05:38 h on individual child contact (1.21%, SD = 00:04:58 h).
Conclusion: For the first time, educators' workflow in day care centres was studied in real time. Some of the educators' self-reported problems were corroborated. The results of this study form a basis upon which further investigations can be built and measures can be developed for an overall improvement of child care.
Im Juli 2000 wurde die Arbeitsgruppe Evidenzbasierte Medizin Frankfurt von einer Gruppe Studierender an der Goethe-Universität gegründet, um die Anwendung der klinisch-wissenschaftlichen Medizin und deren Lehre mit Hilfe der Methoden der Evidenzbasierten Medizin zu verbessern. Aus den mittlerweile 21 freiwilligen zunächst studentischen Kursen in Evidenzbasierter Medizin sind deutschlandweit die ersten verpflichtenden Seminare in Evidenzbasierter Medizin entstanden. Aufgrund des Einsatzes neuer Lehrmethoden von Beginn an und der kontinuierlichen Verbesserung des Seminars sind sowohl formative als auch summative Evaluationen sehr gut. Die im Rahmen der Lehrforschung erhobenen Evaluationsdaten konnten hochrangig publiziert werden. ...